For the past decade we have carried out systematic studies of humoral and cellular immunity in patients with primary immunodeficiency syndromes. Antibody formation to a T cell antigen has been assessed by using bacteriophage 0X 174. Lymphocyte function has been evaluated by response to a standardized battery of mitogens, antigens, and allogeneic cells. B and T cells have been enumerated by rosette formation (E-rosettes and EAC-rosettes) and immunofluorescence. Similar studies have been carried out on human bone marrow transplantation chimeras. We now plan to assess in vitro immunoglobulin and antibody synthesis of B cells to determine actual rates of production, to evaluate the quality (affinity) of antibody as well as amount, and to explore the control mechanisms involved. Both in vitro and in vivo studies will be carried out. The association of enzyme deficiency and combined immune defects has illustrated the importance of studies evaluating purine and pyrimidine metabolism. We have established lymphoblastoid cell lines from patients with immune deficiency syndromes for the study of different biochemical pathways possibly involved in B and T cell differentiation. Attempts will be made to reconstitute the immune function with new therapeutic approaches including transplants of fetal tissue and cultured human thymus, injection of cell extracts (transfer factor) and thymus extracts (thymosin). These studies relate to basic and clinical immunobiology, including resistance to infections, development of malignancy, allergy and collagen diseases.